Abstract:Methylotrophic yeasts are considered as promising cell factories for bio-manufacturing due to their several advantages such as tolerance to low pH and high temperature. In particular, their methanol utilization ability may help to establish a methanol biotransformation process, which will expand the substrate resource for bio-refinery and the product portfolio from methanol. This review summarize current progress on engineering methylotrophic yeasts for production of proteins and chemicals, and compare the strengths and weaknesses with the model yeast Saccharomyces cerevisiae. The challenges and possible solutions in metabolic engineering of methylotrophic yeasts are also discussed. With the developing efficient genetic tools and systems biology, the methylotrophic yeasts should play more important roles in future green bio-manufacturing.